The major aim of this project is to make a comprehensive analysis of the several factors which result in clinical symptoms of Marek's disease herpesvirus-induced neurological disorder in chickens designated transient paralysis (TP). This disease generally occurs in genetically susceptible chickens on the 9th to 11th day after inoculation or exposure to Marek's disease virus (MDV). Symptoms range from mild ataxia to profound coma. Most birds recover in 24 to 72 hours although those that are severely affected may die within the same time period. The factors we will analyze relate to the pathologic, immunologic, viral and genetic aspects of TP. Our previous finding that susceptibility to TP is a recessive trait controlled by major histocompatibility complex (MHC) genes has allowed us to compare genetically susceptible and resistant animals. We found definitve evidence that TP is a disorder of the central nervous system characterized by vasogenic brain edema that may be immune-mediated. The specific aims are to: study the development and disappearance of the causative brain lesion in TP by a sequential study at the light microscope and EM level; study the permeability properties of the blood-brain barrier at critical intervals before, during, and after clinical symptoms of TP occur using the protein-tracer horseradish peroxidase and immunofluorescence; determine the presence or absence of antibody and/or antigen-antibody complexes in the brain parenchyma as well as the choroid plexus by similar techniques; determine the presence or absence of immunoglobulins in the cerebrospinal fluid of affected aninals by polyacrylamide gel electrophoresis and protein staining procedures; study the possible role of complement in TP-brain edema by immunofluorescence and in vivo decomplementation; further study the rigid strain specificity requirements of MDV with respect to their ability to cause TP; and determine, by genetic studies, the specific genetic region of the MHC which controls susceptibility to TP. The attainment of these specific aims may well provide important information with regard to the immunopathology underlying various neurological disorders in man and other species that have a viral etiology.